Mutation scanning methods are important for elucidating the genetic basis of human disease. Single-stranded conformation polymorphism (SSCP)(7) (a bibliography is provided at the end of the written description) is the most widely used mutation scanning method, but its sensitivity varies. Two hybrids between SSCP and Sanger dideoxy sequencing have been developed. These hybrid methods can detect the presence of virtually all mutations. The first hybrid method is dideoxy fingerprinting (ddF). A Sanger reaction is performed with one dideoxy terminator and with one primer to produce a nested set of 5' co-terminal DNA segments, then the segments are denatured and electrophoresed through a non-denaturing gel (10). Mutations can be detected by an alteration in the mobility of at least one of the multiple termination segments that contain the mutation (informative SSCP component). In addition, 6 out of 12 types of possible single-base substitutions result in a gain and/or loss of a dideoxy termination segment at the mutation site (informative dideoxy component). In manual gels, ddF can detect virtually all mutations in a 300-bp region of DNA (1,5,10). The second hybrid method, bidirectional ddF (Bi-ddF) is a modification of ddF in which a cycle sequencing is performed with opposite primers to scan simultaneously for mutations in both directions. Bi-ddF has two important advantages over ddF: (i) the dideoxy component can detect 10 out of 12 types of possible single-base substitutions, and (ii) the SSCP component is on the average more informative because alterations of mobility can be detected in either the downstream or upstream direction. As a result, Bi-ddF can screen 600-bp segments with virtually 100% sensitivity (2,4). However, when these methods are adapted for high G+C regions, smearing of bands sometimes lowers the resolution.